1. Field of the Invention
This invention relates to phenoxazines, particularly to 4-mono-substituted and 4,6-di-substituted phenoxazines, to methods of preparing them, to pharmaceutical compositions containing them and to the use of them as anti-inflammatories. These compounds are lipoxygenase inhibitors.
2. Relevant Art
European Patent Application 0138481 teaches a generic class of phenothiazine compounds useful as leukotriene biosynthesis inhibitors. The specification teaches the substitution of the sulfur atom in the heterocyclic ring with oxygen, thereby producing phenoxazine. Many phenoxazine compounds are disclosed, but none are substituted solely at the 4 position or disubstituted at the 4,6 positions.
In J. Am. Chem. Soc., 80, 2195 (1958) Gilman reports the synthesis phenoxazine-4-carboxylic acid by reacting phenoxazine with n-butyl lithium and then carbon dioxide.
Blank et al, J. Med. Chem., 11, 807 (1968) reports that Gilman's report of phenoxazine-4-carboxylic acid was apparently in error. Based on an analysis of unambiguously synthesized material, Blank demonstrated that Gilman's compound was phenoxazine-1-carboxylic acid. Therefore, despite reports to the contrary, phenoxazine-4-carboxylic acid has not been prepared.